Most attempts of enhancing bone density or formation have traditionally come in the form of increased support and/or the addition of bone graft material to the site of treatment. Such approaches, however, have had only limited success and often fail to provide aid to patients with bone healing deficiencies. For example, spinal fusion protocols typically employ bone autografts, which are fractured into small pieces and placed between the spinal processes to be fused. Such procedures achieve favorable results only in about 40% of treated patients, and the procedures for harvesting graft material render an already invasive procedure even more so.
Efforts to mimic and/or supplement the normal series of events underlying proper bone healing, and also to cure deficiencies associated with these events, have been forthcoming. For example, blood vessel growth has been stimulated in normally healing rabbit mandibular bones by mixing rabbit bone graft material ex vivo with basic fibroblast growth factor (bFGF) and endothelial cells prior to graft implantation (Eppley et al., J. Oral Maxillofac. Surg., 46, 391–98 (1988)). Moreover, in efforts to accelerate fracture healing, osteoblasts and osseous tissue have been infected in vitro and in vivo with vectors delivering DNA encoding osteogenic proteins, such as transforming growth factor-β1 and bone morphogenic protein-2 (Baltzer et al., Gene Ther., 7, 734–79 (2000); Boden et al., Spine, 23, 2486–92 (1998); Gosdstein et al., Clin. Orthopaed. Rel. Res., 355S, S154–62 (1998); Mehrara et al., J. Bone Min. Res., 14(8), 1290–1300 (1999); Riew et al, Calcif. Tissue Int., 63, 357–60 (1998)). However, many such proteins precipitate an inhibitory effect in treated tissues, and some discourage essential neovascularization within such tissues. Moreover, such protocols requiring treatment of rare cells, such as stem cells, depend on the isolation of sufficient quantities of such proteins, which can add yet another level of invasiveness to the procedure, increasing morbidity and post-operative pain and discomfort. Thus, despite improvements in the clinical treatment of bone injuries, there continues to exist a need for improved compositions and/or methods that enhance bone density or formation.